JPS59199654A - Manufacture of fluorinated phenylacetic acid salts and novelfluorinated trichloroehylbenzenes - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides fluorinated β, , β, β-1=! A method for producing salt-resistant phenyl acetic acid fluorinated in the aromatic nucleus at I/X and/or in the side chain from J chloroethylbenzenes, and novel fluorinated 1) chloroethylbenzenes It is something.

3-Trifluoro-methylphenyl and ethyl-3-trifluoro-methylbenz trichlorides are known (see US Pat. No. 4,268,687). The disadvantages of this method are not only the six-step synthesis, but also the need for starting materials which are difficult and require complex techniques.

Vinylidene chloride Meerwein
By hydrolysis of the trichloroethylbenzenes obtained from the arylation, it is possible to produce phenylacetate salts that are not tetramerized. In this process, the phenylacetic acids must first be provided, which must be further esterified in a subsequent reaction step. The disadvantage of this case is that the hydrolysis of trichloroethyl hairzenes using sulfuric acid must be carried out under conditions that promote the progress of side reactions.
The result is that the yield of phenylacetic acid is greatly reduced (V, M, Naidan and A
, V, Dombrovskiy (Dombrovs k +
i) “A, Zh, 0bshch, Khiml, 3
4, 1474, UK). The method uses fluorinated phenylacetic acids or fluorinated phenylacetic acid salts because, for example, 3-β,β,β-trichloroethylbenzofluoride gives only homoisophthalic acid under reaction conditions. Not suitable for manufacturing.

3-Trifluoromethyl-β,β,β-trichloroethylbenzene can also be prepared from vinylidene chloride and the diazonium salt of 3-trifluoromethylaniline (German Published Specification 2°016.809, Example 12)
(see 4).

β,β,β-trichloronitylbenzenes fluorinated in the aromatic nucleus and/or in the side chains are
We have now discovered a process for the preparation of phenylacetates fluorinated in the aromatic nucleus and/or in the side chains, characterized in that they are reacted with 1.1 and then with an acid.

For example, fluorinated trichloroethyl hairzenes of the following formula are suitable for use in the method according to the invention: R1 lbi.

In the formula, R1 is a group -CF3,0CF3-1 OCHF2, SCF3. S CHF 2
, -CH2-CF3, -CH2-CH2-CF3, -CF (CR3-) 2, -〇〇F2-CHFCl, -5CF2-CHFCl, -0CF2-CF2H or -3CF2-CF2H, and R2 represents hydrogen, halogen, alkyl, alkoxy, nitro or one of the groups mentioned for R□, or Rli and R2 together form the group -0-CF2-0-1 OCF2 CF2 0-1 - O-CF 2- CHF 0-1-O-CF2-
CFCl -0-1 -〇 -CF2- CH20- or 0-CF20
represents one type of CF2-].

When R2 represents halogen in this formula, it preferably represents fluorine, chlorine or bromine, particularly preferably fluorine or chlorine. When R2 represents alkyl in this formula, it preferably represents C1-C4-alkyl, and when R2 represents alkoxy in this formula, it preferably represents C1-04-alkoxy.

R1 is preferably a group -CFa, 0CF3-1-OCH
F2, -SCF3, -SCHF2,
CH2CF a , OCF 2 CHF Cl
, OCF2CF2H or -5CF2-CF
Represents one type of 2H.

R2 preferably represents hydrogen, fluorine, chlorine, methyl, ethyl, methoxy, ethoxy or one of the groups indicated as suitable for R□.

When R1 and R2 together represent a divalent group, Ro and R2 together preferably represent 10-CF
2-0-1-0-CF2-CF2-0-1-0-CF2
-CHF-0-1-〇-CF2-CFCl-0-, mata represents one type of -0-CF2-0-CF2-.

The β,β,β-trichloroethylbenzenes mentioned above are particularly preferably used in the process according to the invention: ,'〆1substituent(s) position(s)--Once I CF34 CF33 CF3C124 cF3CI 3 60F30F
33 5 FF 24CF30
40F30
2CF3S
4-0-CF2-o-34-O-CF2(:HF-0-34-OCF2-CI"2-0-3
4]-The blank column in R2 is H.

A wide variety of aliphatic or aromatic alcoholates can be used as alcoholates for the reaction according to the invention. The alcoholates preferably used have 1 to 1 carbon atoms.
It is derived from the aliphatic alcohols of No. 4, such as alkanols, and contains an alkali metal and/or alkaline earth metal ion as a counterion to the alcohol group. Sodium methylate is particularly preferably used.

! ! According to the law, alcoholates can be used in any desired manner. The use of a molar excess of alcohol 1, i.e. 3 moles per mole of fluorinated β, β, β-trichloroethylbenzene. 3.1 to 5 mol of alcoholate are used per i.lichloroethylbenzene.

The alcohol-1 reaction is generally carried out in the presence of a solvent. Examples of suitable solvents are aprotic solvents, such as ethers, such as dienal ethers, glycol dimethyl ether and dioxane; sulfones, such as tetramethylene sulfone; and also carboxamides, such as dimethylformamide and diethylacetamide,
It is.

Preferred solvents are alcohols, which may be used as appropriate.
- in combination with one of the aprotic solvents listed below. Particularly suitably, the solvent used is an alcohol corresponding to the alcoholate used, ie for example methanol when using sodium methylate. The solvent or solvents can be added directly to the reaction. Preferably, an alcoholic solution of Alcole-1 is added and no other solvent is used.

The amount of solvent can vary within wide limits, and preferably the solvent is used in an amount at least sufficient to provide an easily stirrable reaction mixture.

The reaction with the alcoholate can be carried out, for example, at a temperature in the range from 20 to 120°C. This reaction is generally carried out at atmospheric pressure, but it can also be carried out under reduced or elevated pressure.

Although it is not necessary to relay the reaction products formed by the reaction of the fluorinated β,β,β-trichloroethylbenzenes with the alkoxylates, it can be carried out, for example, by distillation, if desired. Fluorinated β, β, β
-Products from the reaction of -trichloroethylbenzenes with alcoholates, preferably the total reaction mixture formed from the reaction of fluorinated β,β,β-trichloroethylbenzenes with alcoholates-1. According to the invention, acid and anti-14
λ: Yes. Generally, the acid is added at r-' such that a pH of less than 5 is produced. Preferably, the pFl value is brought to a range of 4.5 to 1 using acid.

Suitable acids include a wide variety of acids with which the above pH values can be achieved. Strong inorganic acids, such as hydrochloric acid or sulfuric acid, are preferably used.

Sulfuric acid is particularly preferably used. It will be done.

The reaction with acid can be carried out, for example, at a temperature in the range from 20 to 120°C. Generally, the process is carried out as follows: the acid is first heated, e.g.
It is added with appropriate cooling at a relatively low temperature, such as in a circle, and then the reaction with the acid is completed at a relatively high temperature, such as within the range of 50 to 120°C.

Reaction with acid: The fluorinated phenylacetic acids subsequently present in the reaction mixture can be relayed in various ways, for example by extraction or distillation or by a combination of distillation and extraction methods.

In a preferred method for treating the reaction mixture obtained after the reaction with the alcoholate followed by the reaction with the acid, without entraining intermediate products, the following process example is first used: The alcohol corresponding to the alcoholate and the alcohol optionally used as solvent and any other solvents are separated by distillation, optionally under reduced pressure. Add at least enough hanging wood to the remaining bottom product to produce a distinct two-phase system. The aqueous phase is then discarded and the organic phase is extracted with winder solvent. Examples of solvents suitable for this purpose are chlorinated hydrocarbons, especially dichloromethane. The solvent is then removed from the extract formed, for example by 15 distillations under reduced pressure, and the remaining residue is distilled in vacuo, for example at a pressure in the range from 5 to 50 mbar.

After treating the reaction mixture in this or other manner, the fluorinated phenylacetates corresponding to the fluorinated β,β,β-trichloroethylbenzene used and the alcoholate used are obtained. If alcohols that do not correspond to the alcohol-11 used are used as solvents, mixtures of different fluorinated phenylacetates can be prepared.

Phenyl acetates fluorinated in the aromatic core and/or in the side chains according to the invention can be obtained in good yields.
1°Ijf is quite surprising since it was expected that hydrolysis of the fluorine-containing substituents would occur during the process according to the invention.

The present invention further provides 3-trifluoromethyl-β.

Other than β, β-trichloroethylbenzene compounds, compounds of the formula [wherein R1 is a group -CF3.0CF3-2 OCHF 2 , SCF 3 , SCHF
2.

represents one of CH2CF3, -CH2-CH2-CF3, 10F (C', F3)2, -OCF2CHFCl, -5CF2-CHFC1, OCF2CF2H or SCF2CF2H, and R2 represents hydrogen, halogen, alkyl, alkoxy, nitro or one of the groups listed in F1, or R1 and R2 together form the group -C)-CF2-0-1 -O-CF2 -CF2-C)-1 -O-CF2CHF0-1 -O-CF2-CFCl-0-1 -O-CF2-CH2-0- or a new fluorine of J representing one of OCF20CF2- It also relates to β, β, β-trichloroethylbenzenes.

When R2 represents halogen in this formula, it preferably represents fluorine, chlorine or bromine, particularly preferably fluorine or chlorine. In this formula, when R2 represents alkyl, it represents &-f suitably C1-04-alkyl,
And in this formula, when R2 represents alkoxy, it preferably represents C,-C,-alkoxy.

R, is preferably a group -CF3.0CF3-1-0CHF2
, -5CF3.5CHF2, -CH2-CF3,
0CF2 CHFCl, -0CF2-CF3
I or -5CF2-CF3I.

R2 is preferably hydrogen, fluorine, chlorine 1. methyl, ethyl,
Methoxy, ethoxy or R1 represents one of the groups indicated as suitable.

However, when R represents a CF3 group in the 3-position with respect to the β, β, β-trichloroethyl group, R2 does not represent hydrogen.

When R1 and R2 together represent a divalent group, R□ and R2 together preferably represent -0-C
F2-0-1-0-CF2-CF2-0-1-0-C
F2CHF 0-l-0-CF2-CFCI-
〇-, Mata represents one type of -0-CF2-CF2-0-.

Particularly suitable fluorinated β, β, β-trichloroethylbenzenes are: ? l sushi 0u-t(
Type) R, Dan L CF3 C124 CF3C16 CF3CI 3
5FF
40F30
4CF30
2 to F 3 S
4-0. -CF2-o-3
4 O-CF2 (:HF-0-34 O-CF2-CF 2-0-
3 4O-CF20PCI-0-34 OF,
40CHF2
4, the blank column of R2 is H.

Anilines, e.g. 3-trifluoro-methylaniline, can be diazotized by reaction with nitrite in the presence of hydrochloric acid, and diathunium '2A thus formed can be diazotized in the presence of acetone and a catalyst such as copper chloride. The reaction with vinylidene chloride below gives the corresponding β, β,
It is known to contain β-trichloroethylbenzenes, such as 3-trifluoromethyl groups β,β,β-I-lichloroethylbenzene (for example, J, f,
pral (, Chemie, 152. 237
-266i (1939) and German Publication Specification 2,0
16.890).

Novel fluorinated β, β, β-trichloroethylbenzenes can be prepared in a similar manner by formula [wherein R1 and R2 have the meanings given in H, but when R1 is NH2
When representing a trifluoromethyl group at the 3-position with respect to the group, R2 does not represent hydrogen]. The diazonium salt of the aniline used is then diazotized and the resulting diazonium salt of the aniline used is reacted with hynylidene dichloride at a temperature of, for example, 20 to 80° C. in the presence of acetone and chloride. I will be II.

Novel fluorinated β,β,β-trichloroethylpenzes are fluorinated in the aromatic nucleus and/or in the side chains, which are safe intermediates for the production of value removers. These compounds are valuable intermediates, since they can be converted into phenylacetic acid salts in a simple manner and with good yields (for example, German Published Application No. 2,537). , 753 and German Publication Specification 2,628
, 992).

From a general point of view, this process is a particularly advantageous preparation process for phenylacetate salts fluorinated in the aromatic nucleus and/or in the side chains; and/or starting from anilines fluorinated in the side chain, 3-trifluoro-methyl-
β, β.

The corresponding β, β, β-trichloroethylbenzenes, which are new materials except β-trichloroethylbenzene, are prepared and these are then converted to the corresponding phenylacetates.

The first embodiment is intended to illustrate the present invention, but is not intended to limit it in any way.

242g of T-grade 3-trifluoromethylaniline
00 ml of water and 450 ml of 37% strength hydrochloric acid were initially added at 0.degree. C. and then re-diasotated by dropwise addition of a solution of 103.5 g of sodium nitrite in 330 ml of water. By cooling, the temperature is reduced to -5 to
'c. After the addition of the thorium nitrite solution was complete, stirring was continued for 1 hour and amidosulfonic acid was added to decompose any nitrite that may still be present. The resulting cooled dianium melt was passed through a filter, 200 ml of acetone, 45
It was added into a mixture of 0g of vinylizo +22ide/and 15g of copper chloride. The mixture was stirred at 25-30°C until gas evolution was complete and then kept under reflux for a further 2 hours. After distilling off excess hnylidene chloride and acetone, the bottom a] mechanical phase is separated and the resulting crude 3-trifluoromethyl-β,β,β-trichloroethylbenzene is transferred to column 1-5 in distillation. It was purified by The 3-trifluoromethyl-β,β,β-trichloroethylbenzene thus obtained has a boiling point of 112 °C at 20 mbar and a refractive index of 2.6 of 1.4878 and a theoretical value of Obtained with a yield of 67%.

Hiba Masue: ” β corresponding to other fluorinated anilines in a manner corresponding to that described in Example 1.

It was converted into β,β-trichloroethylbenzenes. The anilines used, the obtained β, β, β-trichloroethylbenzene furnace, and the produced β, β.

Table 1 shows the physical data measured for β-trichloroenalbenzenes and the yields at which they were obtained.
summarized in.

135'.

γ9 10 75 g of 3-trifluoromethyl-β,β,β-trichloroethylhensen in 101O0 methanol are first added and 135 ml of a 30% strength solution of sodium methylate in methanol are added to this 117 The mixture was added dropwise at room temperature. When the addition was complete, the mixture was boiled at reflux for 3 hours, then cooled to 20°C,
30 ml (1) of e&iW was added to the boiler, the mixture was boiled for 1 hour, and then methanol was removed by distillation. Add enough Fl wood to the remaining product to form a distinct phase, extract the right rock phase with dichloromethane, remove dichloromethane by distillation, and methyl 3-trifluoromethylphenylacetate is produced by vacuum distillation. 83
% yield. The boiling point of methyl 3-trifluoromethylphenylacetate was 97-100°C/15 mbar and its refractive index n was 1°4570.

Other fluorinated anilines were converted to the corresponding fluorinated methyl phenylacetates in a manner corresponding to that described in Example 10. The fluorinated β used
, β, β-triccholoethylhensenes, fluorinated methyl phenylacetates, and the physical data determined for the produced Japanese methyl phenylacetates, and these are The yields are summarized in Table 2.j-9\Example 19 3-trifluoromethyl-β,
β, β-trichloroethylbenzene and potassium n-
Butyrate 3-trifluoromethylphenylacetic acid N
-Butyl was obtained. Boiling point at 18 mbar +1
22-1.24°C; n wisdom: 1.4850°

Claims (1)

[Claims] 1. characterized in that β, β, β-trichloroethylbenzenes fluorinated in the aromatic nucleus and/or in the side chain are reacted with an alcoholate and then with an acid. A process for producing phenylacetates fluorinated at the aromatic nucleus and/or at the side chain rp. 2. The fluorinated β, β, β-trichloroethyl benzene/formula used [wherein R, is a group -CF3.0CF3-1 -OCHF2, -3CF3, 5CHF2, -CH2
-CF3, CH2CH2CF3, -CF(CF3)2, -CF2-CHFCI, -3CF2-CHFCl, -CF2-CF2H or -5CF, -CF2H, and R2 is hydrogen, halogen, alkyl, alkoxy, nitro or one of the groups listed in R1, or R1 and R2 together represent a group -0-CF, -0-1 -O-CF2-CF2-0-1 -O -CF2-CHF-0-. -0-CF2-CFCI-C)-7 -O-CF2-CH2-0- or 0CF20-CF2-] The method according to claim 1. 3.1 moles of fluorinated β, β, β-! Claim 1 or 2, characterized in that at least 3 mol of alcoholate is used per dichloroethylhenzene.
The method described in section. 4. The method according to claims 1 to 3, characterized in that an alkali metal and/or alkaline earth metal alcoholate of an aliphatic alcohol having 1 to 4 carbon atoms is used. 5. The method according to claims 1 to 4, characterized in that the reaction with flucorate is carried out in the presence of an aprotic solvent and/or in the presence of an alcohol;
. 6. Process according to claims 1 to 5, characterized in that the reaction with the alcoholate is carried out at a temperature in the range from 20 to 120°C. 7. The amount of acid added for reaction with the liquor has a pH lower than 5.
A method according to claims 1 to 6q4, characterized in that the method is such as to yield a value. 8. The method according to claims 1 to 7, characterized in that the reaction with an acid is carried out using a strong inorganic acid. 9. Claims 1 to 8, characterized in that the reaction with the acid is carried out at a temperature within the range of 20 to 120°C.
The method described in section. jo, 3-1 Lifluoromethyl-β,β,β-trichloroedylbenzene compound other than the compound [wherein R1 is a group -CF3.0CF3-1-OCHF2, SCF3.5CHF2]
. -CH2CF3, CH2CH2CF3, -CF (CFa)2, -QCF2-CHFCl, -5CF, -CHFcl. represents one of -CF2-CF2H or -3CF2-CF2H, and R2 represents hydrogen, halogen, alkyl, alkoxy, nitro or one of the groups mentioned for R1, or R□ and R2 Together the groups 10 CF2 0-1 -O-CF2-CF2-0-1 -O-CF2-CHF-0-1 -O-CF2-CFCl-0-1 -OCF2 CH20- or -0-CF2 -0-CF2-'' fluorinated β, β, β-trichloroethylbenzenes.